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上呼吸道黏膜免疫系统和黏膜疫苗的新进展。

The mucosal immune system of the upper respiratory tract and recent progress in mucosal vaccines.

机构信息

Department of Otolaryngology, Head and Neck Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.

出版信息

Auris Nasus Larynx. 2022 Feb;49(1):1-10. doi: 10.1016/j.anl.2021.07.003. Epub 2021 Jul 23.

DOI:10.1016/j.anl.2021.07.003
PMID:34304944
Abstract

The mucosal immune system prevents microorganism invasion through mucosal surfaces and consists of inductive and effector sites. Nasopharynx-associated lymphoid tissue (NALT) functions as an inductive site, inducing mucosal immune responses in the upper respiratory tract. It follows that intranasal vaccines may prevent upper respiratory infections. To induce and enhance the immune response by administering inactivated antigens intranasally, mucosal adjuvants have been developed, including mutant cholera toxin and cationic cholesteryl pullulan nanogel, which do not accumulate in the central nervous system. Moreover, multivalent pneumococcal polysaccharide conjugate vaccines are used to prevent invasive pneumococcal infections and otitis media, although they only provide moderate protection against acute otitis media because non-vaccine serotypes of Streptococcus pneumoniae and Haemophilus influenzae also cause this infection. To address this problem, pneumococcal surface protein A of S. pneumoniae and P6 of H. influenzae are used as broad-spectrum vaccine antigens. Alternatively, phosphorylcholine (PC) is present in the cell walls of both gram-positive and gram-negative bacteria and induces immune responses through antigenic activity. The significant effects of PC as a mucosal vaccine have been demonstrated through intranasal and sublingual immunization in mice. Furthermore, intranasal administration of PC reverses increases in IgE levels and prevents allergic rhinitis. After immunization with pneumococcal polysaccharide conjugate vaccine, intranasal immunization with PC boosts immune responses to vaccine strains and to PC itself. Thus, PC may be useful as a mucosal vaccine to prevent upper respiratory infections and allergic rhinitis, and it could be used as a booster to the currently used pneumococcal vaccine as it protects against non-vaccine strains.

摘要

黏膜免疫系统通过黏膜表面防止微生物入侵,由诱导和效应部位组成。鼻咽相关淋巴组织 (NALT) 作为诱导部位,在上呼吸道诱导黏膜免疫反应。因此,鼻内疫苗可能预防上呼吸道感染。为了通过鼻内给予失活抗原来诱导和增强免疫反应,已经开发了黏膜佐剂,包括突变霍乱毒素和阳离子胆甾醇 pullulan 纳米凝胶,它们不会在中枢神经系统中积累。此外,多价肺炎球菌多糖结合疫苗用于预防侵袭性肺炎球菌感染和中耳炎,尽管它们仅对急性中耳炎提供中度保护,因为肺炎链球菌和流感嗜血杆菌的非疫苗血清型也会引起这种感染。为了解决这个问题,肺炎球菌表面蛋白 A 和流感嗜血杆菌 P6 被用作广谱疫苗抗原。或者,磷酸胆碱 (PC) 存在于革兰氏阳性和革兰氏阴性细菌的细胞壁中,并通过抗原活性诱导免疫反应。PC 作为黏膜疫苗的显著效果已通过在小鼠中的鼻内和舌下免疫得到证明。此外,鼻内给予 PC 可逆转 IgE 水平的升高并预防过敏性鼻炎。在接种肺炎球菌多糖结合疫苗后,用 PC 进行鼻内免疫可增强对疫苗株和 PC 自身的免疫反应。因此,PC 可用作预防上呼吸道感染和过敏性鼻炎的黏膜疫苗,并且可以作为目前使用的肺炎球菌疫苗的增强剂,因为它可以预防非疫苗株。

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